-
Tong-You W Wei,
Chi-Chang Juan, Jiun-Yi Hisa,
Li-Jen Su,
Yuan-Chii G Lee,
Hsiang-Yun Chou,
Jo-Mei M Chen,
Yu-Chung Wu,
Shao-Chih Chiu,
Chung-Ping Hsu,
Kuo-Lin Liu,
Chang-Tze R Yu
[show abstract]
[hide abstract]
ABSTRACT: Increasing evidence suggests that PRMT5, a protein arginine methyltransferase, is involved in tumorigenesis. However, no systematic research has demonstrated the cell-transforming activity of PRMT5. We investigated the involvement of PRMT5 in tumor formation. First, we showed that PRMT5 was associated with many human cancers, through statistical analysis of microarray data in the NCBI GEO database. Overexpression of ectopic PRMT5 per se or its specific shRNA enhanced or reduced cell growth under conditions of normal or low concentrations of serum, low cell density, and poor cell attachment. A stable clone that expressed exogenous PRMT5 formed tumors in nude mice, which demonstrated that PRMT5 is a potential oncoprotein. PRMT5 accelerated cell cycle progression through G1 phase and modulated regulators of G1; for example, it upregulated cyclin-dependent kinase (CDK) 4, CDK6, and cyclins D1, D2 and E1, and inactivated retinoblastoma protein (Rb). Moreover, PRMT5 activated phosphoinositide 3-kinase (PI3K)/AKT and suppressed c-Jun N-terminal kinase (JNK)/c-Jun signaling cascades. However, only inhibition of PI3K activity, and not overexpression of JNK, blocked PRMT5-induced cell proliferation. Further analysis of PRMT5 expression in 64 samples of human lung cancer tissues by microarray and western blot analysis revealed a tight association of PRMT5 with lung cancer. Knockdown of PRMT5 retarded cell growth of lung cancer cell lines A549 and H1299. In conclusion, to the best of our knowledge, we have characterized the cell-transforming activity of PRMT5 and delineated its underlying mechanisms for the first time.
Cancer Science 06/2012; 103(9):1640-50. · 3.33 Impact Factor
-
Shi-Yi Yang,
Tsung-Ying Yang,
Yao-Jen Li,
Kun-Chieh Chen,
Kuo-Meng Liao,
Kuo-Hsuan Hsu,
Chi-Ren Tsai,
Chih-Yi Chen,
Chung-Ping Hsu, Jiun-Yi Hsia, [......],
Ying-Huang Tsai,
Kuan-Yu Chen,
Ming-Shyan Huang,
Wu-Chou Su,
Yuh-Min Chen,
Chao A Hsiung,
Chen-Yang Shen,
Gee-Chen Chang,
Pan-Chyr Yang,
Chien-Jen Chen
[show abstract]
[hide abstract]
ABSTRACT: We explored potential associations between genetic polymorphisms in genes related to DNA repair and detoxification metabolism and epidermal growth factor receptor (EGFR) mutations in a cohort of 410 never-smoking patients with lung adenocarcinoma. Multivariate-adjusted odds ratios (aORs) and corresponding 95% confidence intervals (CI) of EGFR mutation status in association with the genotypes of DNA repair and detoxification metabolism genes were evaluated using logistic regression analysis. We found an association between in-frame deletion in EGFR exon 19 and a single nucleotide polymorphism (SNP) rs1800566C/T located in NQO1 (aOR, 2.2 with 95% CI, 1.0-4.8) in female never-smokers. The SNP rs744154C/G in ERCC4 was also associated with the EGFR exon 19 in-frame deletion both in never-smokers (aOR, 1.7 with 95% CI, 1.0-3.0) and female never-smokers (aOR, 1.9 with 95% CI, 1.0-3.6). Although the association was marginally significant in multivariate logistic regression analysis, the A/A genotype of rs1047840 in EXO1 was associated with a 7.6-fold increase in the occurrence of the EGFR exon 19 in-frame deletion in female never-smokers. Moreover, risk alleles in NQO1, ERCC4 and EXO1 were associated with an increasing aOR of the EGFR exon 19 in-frame deletion both in never-smokers (p = 0.007 for trend) and female never-smokers (p = 0.002 for trend). Our findings suggest that the in-frame deletion in EGFR exon 19 is associated with polymorphisms in DNA repair and detoxification metabolism genes in never-smoking lung adenocarcinoma patients, especially in females.
International Journal of Cancer 05/2012; · 5.44 Impact Factor
-
Shinsheng Yuan,
Sung-Liang Yu,
Hsuan-Yu Chen,
Yi-Chiung Hsu,
Kang-Yi Su,
Huei-Wen Chen,
Chih-Yi Chen,
Chong-Jen Yu,
Jin-Yuan Shih,
Yih-Leong Chang, [......],
Yi-Ling Lai,
Chu-Chun Hsu,
Tai-Ching Lin,
Tsung-Ying Yang,
Kun-Cheieh Chen,
Kuo-Hsuan Hsu,
Jeremy J W Chen,
Gee-Chen Chang,
Ker-Chau Li,
Pan-Chyr Yang
[show abstract]
[hide abstract]
ABSTRACT: Although epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been proven more effective for patients with lung adenocarcinoma with EGFR-activating mutation rather than wild type, the former group still includes approximately 30% nonresponders. The molecular basis of this substantial response heterogeneity is unknown. Our purpose was to seek molecular aberrations contributing to disease progression at the genome-wide level and identify the prognostic signature unique to patients with EGFR-activating mutation.
We first investigated the molecular differences between tumors with EGFR-activating mutation and wild-type tumors by conducting high-density array comparative genomic hybridization on a collection of 138 adenocarcinoma tissues. We then used an independent group of 114 patients to validate the clinical relevance of copy-number alterations (CNAs) in predicting overall and disease-free survival. Finally, focusing on 23 patients with EGFR mutation receiving EGFR-TKI treatment, we investigated the association between CNAs and response to EGFR-TKIs.
We identified chromosome regions with differential CNAs between tumors with EGFR-activating mutation and wild-type tumors and found the aberration sites to cluster highly on chromosome 7p. A cluster of six representative chromosome 7p genes predicted overall and disease-free survival for patients with EGFR-activating mutation but not for those with wild type. Importantly, simultaneous presence of more genes with increased CNAs in this cluster correlated with less favorable response to EGFR-TKIs in patients with EGFR-activating mutation.
Our results shed light on why responses to EGFR-TKIs are heterogeneous among patients with EGFR-activating mutation. They may lead to better patient management in this population.
Journal of Clinical Oncology 08/2011; 29(25):3435-42. · 18.37 Impact Factor
-
Kuo-Hsuan Hsu,
Kun-Chieh Chen,
Tsung-Ying Yang,
Yi-Chen Yeh,
Teh-Ying Chou,
Hsuan-Yu Chen,
Chi-Ren Tsai,
Chih-Yi Chen,
Chung-Ping Hsu, Jiun-Yi Hsia,
Cheng-Yen Chuang,
Ying-Huang Tsai,
Kuan-Yu Chen,
Ming-Shyan Huang,
Wu-Chou Su,
Yuh-Min Chen,
Chao A Hsiung,
Gee-Chen Chang,
Chien-Jen Chen,
Pan-Chyr Yang
[show abstract]
[hide abstract]
ABSTRACT: Early lung adenocarcinoma may present with ground-glass opacity (GGO) component in computed tomography (CT) scan. Epidermal growth factor receptor (EGFR) mutation had been reported in patients with lung cancer with GGO patterns. Nevertheless, the correlation between clinical characteristics, CT image patterns, and EGFR mutation status was indeterminate.
Patients with stage I lung adenocarcinoma with tumor lesions less than 3 cm were included and classified into pure GGO, part-solid, and solid patterns by CT scan images. All patients had EGFR mutation test from frozen tumors. Available paraffin-embedded archival tissues were microdissected into three different locations similar to CT images with central and peripheral parts of tumor, and adjacent normal part for EGFR mutation tests.
Totally, 162 patients were analyzed, 90 women and 72 men, and 128 nonsmokers. The patients included 35 (21.6%) pure GGO, 41 (25.3%) part-solid, and 86 (53.1%) solid lesions. The EGFR mutation rate was 64.2% (n = 104). Analysis of the correlation between CT image patterns and EGFR mutation, the less GGO ratio had more typical mutation, especially L858R (p = 0.037). In 45 microdissected tumors, the central and peripheral parts had the same EGFR mutation status. In adjacent normal parts, 5 of 32 (15.6%) EGFR mutant patients had identical mutation but none in nonmutant patients.
In stage I lung adenocarcinoma, typical mutation, especially L858R was detected more frequent in invasive solid pattern and significantly less in pure GGO pattern. EGFR mutation is an early event in the pathogenesis of lung adenocarcinoma and may facilitate the tumor into aggressive behavior.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 06/2011; 6(6):1066-72. · 4.55 Impact Factor
-
Chang-Tze Ricky Yu, Jiun-Yi Hsia,
Yun-Chih Hseih,
Li-Jen Su,
Tien-Chiang Lee,
Chia-Feng Ku,
Ke-Shin Chen,
Jou-May Maureen Chen,
Tong-You Wade Wei,
Yuan-Chii Gladys Lee,
Chi-Ying F Huang,
Yu-Chung Wu,
Chiou-Ying Yang,
Shih-Lan Hsu
[show abstract]
[hide abstract]
ABSTRACT: In an attempt to search for genes with abnormal expression in cancers, Suppressed in Lung Cancer (SLAN, also known as KIAA0256) is found underexpressed in human lung cancer tissues by quantitative real-time PCR (Q-RT-PCR). The study set out to characterize SLAN protein and explore its cellular functions.
SLAN or its specific short hairpin RNA, full length or various deletion mutants were overexpressed in 293T or lung cancer cell lines, and cell proliferation, cell cycle, mitosis progression, and spindle configuration were surveyed.
SLAN and its deletion mutants are localized to many subcellular locations such as endoplasmic reticulum (ER), nucleus, nucleolus, spindle pole and midbody, suggesting SLAN may function as a multifunctional protein. Overexpression of SLAN per se or its short hairpin RNAs (shRNAs) inhibits or accelerates cell proliferation through prolonging or shortening mitosis. Time-lapse microscopic recording reveals that cells overexpressing exogenous SLAN are arrested in mitosis or cannot undergo cytokinesis. SLAN 2-551 mutants drastically arrest cells in mitosis, where α- and γ-tubulin are disorganized. SLAN employs C-terminal to interact with Aurora-A, a key mitosis regulator and an oncogenic kinase associated with a wide range of human cancers. SLAN negatively regulates the activity of Aurora-A by directly inhibiting kinase activity in vitro or reducing the level of active Aurora-A in cells. SLAN is frequently reduced in lung cancer tissues overexpressing Aurora-A, arguing for the necessity to suppress SLAN during the Aurora-A-associated cancer formation.
Taken together, we have identified a novel protein SLAN downregulated in lung caner, having multiple subcellular localization including spindle matrix and midbody, inhibiting cell proliferation and Aurora-A.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 06/2011; 6(6):988-97. · 4.55 Impact Factor
-
Shi-Yi Yang,
Tsung-Ying Yang,
Kun-Chieh Chen,
Yao-Jen Li,
Kuo-Hsuan Hsu,
Chi-Rne Tsai,
Chih-Yi Chen,
Chung-Ping Hsu, Jiun-Yi Hsia,
Cheng-Yen Chuang,
Ying-Huang Tsai,
Kuan-Yu Chen,
Ming-Shyan Huang,
Wu-Chou Su,
Yuh-Min Chen,
Chao A Hsiung,
Chen-Yang Shen,
Gee-Chen Chang,
Pan-Chyr Yang,
Chien-Jen Chen
[show abstract]
[hide abstract]
ABSTRACT: To assess whether polymorphisms of genes related to estrogen biosynthesis and metabolism are associated with EGFR mutations.
We studied 617 patients with lung adenocarcinoma, including 302 never-smoking women. On the basis of multiple candidate genes approach, the effects of polymorphisms of CYP17, CYP19A1, ERα, and COMT in association with the occurrence of EGFR mutations were evaluated using logistic regression analysis.
In female never-smokers, significant associations with EGFR L858R mutation were found for the tetranucleotide (TTTA)(n) repeats in CYP19A1 (odds ratio, 2.6; 95%CI, 1.2-5.7 for 1 or 2 alleles with (TTTA)(n) repeats >7 compared with both alleles with (TTTA)(n) repeats ≤ 7), and the rs2234693 in ERα (OR, 2.1; 95% CI, 1.1-4.0 for C/T and C/C genotypes compared with T/T genotype). The C/C genotype (vs. T/T genotype) of ERα was significantly associated with EGFR L858R mutation (OR, 3.0; 95% CI, 1.1-8.1), in-frame deletion (OR, 2.9; 95% CI, 1.1-7.6) and other mutations (OR, 4.3; 95% CI, 1.3-14.0). The genotype of COMT rs4680 was significantly associated with EGFR L858R mutation in female and male never-smokers showing OR's (95% CI) of 1.8 (1.0-3.2) and 3.6 (1.1-11.3), respectively, for genotypes G/A and G/G compared with genotype A/A. The number of risk alleles of CYP17, CYP19A1, ERα, and COMT was associated with an increasing OR of EGFR L858R mutation in female never-smokers (P = 0.0002 for trend).
The L858R mutation of EGFR is associated with polymorphisms of genes related to estrogen biosynthesis and metabolism in never-smoking female lung adenocarcinoma patients.
Clinical Cancer Research 02/2011; 17(8):2149-58. · 7.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Calcium-binding tyrosine phosphorylation regulated protein (CABYR), a family of isoforms resulting from alternative splicing, has been identified as a cancer/testis antigen (CT88) in lung cancer and hypothesized to be a promising target for immunotherapy. Here, we report the expression of CABYR in various cancer tissues/cell lines. Expression profiles of individual isoforms were different among cancers. Furthermore, protein and mRNA levels did not correlate for individual isoforms. While CABYR-c/d were the most abundant splicing variants, CABYR-a was the predominant protein isoform. Finally, CABYR-a, but not CABYR-c, was found to interact with α-enolase in vivo. Collectively, the data indicate that CABYR is a CT antigen widely expressed in diverse cancer cells. However, individual protein isoforms may be differentially regulated by post-transcriptional and post-translational mechanisms and may have a unique role in carcinogenesis. The protein expression pattern of various CABYR isoforms is important with regard to the consideration of using CABYR as a target antigen for the development of vaccines for cancer therapy.
Oncology Reports 01/2011; 25(4):1169-75. · 1.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Pneumoscrotum, the accumulation of air inside the scrotum, is a rare complication associated with blunt chest trauma. We report a case of severe subcutaneous emphysema, pneumothorax, pneumomediastinum, pneumopericardium, and pneumoscrotum after blunt chest trauma in a 44-year-old man. He presented with progressive swelling of the neck that descended to the chest, abdomen, both legs, and scrotum. Radiography and computed tomography of the chest and abdomen confirmed the diagnosis of a tracheal injury complicated by severe subcutaneous emphysema, pneumothorax, pneumomediastinum, pneumopericardium, and pneumoscrotum. Primary repair of the tracheal injury was performed, and he was weaned successfully from the ventilator by day 5. He was discharged on day 7.
Urology 03/2010; 77(1):75-6. · 2.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Our objective was to identify surgical-pathologic factors affecting prognosis in stage IB non-small cell lung cancers.
Between 1997 and 2006, a cohort of 272 cases of pT2 N0 M0 stage lung cancer were retrospectively analyzed. The patients included 70 women and 202 men with a mean age of 67.0 years. The surgical resections included pneumonectomy in 4, bilobectomy or lobectomy in 217, and limited resections in another 51. The impact of surgical-pathologic characteristics on survival, including cell type, tumor differentiation, tumor size, depth of visceral pleural invasion, type of surgical resection, and extent of lymphadenectomy on patient survival, was compared accordingly.
Tumor types included adenocarcinoma/bronchioloalveolar carcinoma in 142, squamous cell carcinoma in 100, and others in 30. Cell differentiations were classified as well, moderately, and poorly differentiated in 23, 151, and 92 cases, respectively. The mean tumor size was 3.9 cm in diameter, and the average resected lymph node number was 14.3. Direct visceral pleural or subpleural invasions (<1 mm) were found in 134 and 42 cases, respectively. Angiolymphatic invasions were seen in 26 cases, and positive tumor margins were found in 14 cases. The overall 5-year and 10-year survivals were 59.5% and 41.3%, respectively. Good prognostic factors using univariate analysis included female gender, nonlimited resection, well-differentiated tumor, no angiolymphatic invasion, smaller size (<or=3 cm), and numbers of nodes retrieved (>14 nodes). However, the Cox proportional hazard model revealed female gender, well-differentiated tumor, no pleural involvement, no angiolymphatic invasion, and more than 14 nodes retrieved as independent good prognostic factors.
Stage IB lung cancer can be treated by standard pulmonary resection accompanied by adequate mediastinal lymphadenectomy. Owing to the heterogeneity of stage IB lung cancer and the fact that prognosis can be affected by many surgical-pathologic factors, refinement of the current TNM staging criteria may be needed.
The Journal of thoracic and cardiovascular surgery 09/2009; 138(2):426-33. · 3.41 Impact Factor
-
Fen-Hwa Wong,
Chi-Ying F Huang,
Li-Jen Su,
Yu-Chung Wu,
Yong-Shiang Lin, Jiun-Yi Hsia,
Hsin-Ting Tsai,
Sheng-An Lee,
Chi-Hung Lin,
Cheng-Hwai Tzeng,
Po-Min Chen,
Yann-Jan Chen,
Shu-Ching Liang,
Jin-Mei Lai,
Chueh-Chuan Yen
[show abstract]
[hide abstract]
ABSTRACT: Microarray profiling of 15 adjacent normal/tumor-matched esophageal squamous cell carcinoma (ESCC) specimens identified 40 up-regulated and 95 down-regulated genes. Verification of the microarray measurement by quantitative real-time reverse transcription PCR in the same set of samples as well as an additional 15 normal/tumor-matched samples revealed >95% consistency. These signatures can also be used to classify a recently reported ESCC microarray dataset. Moreover, these molecular signatures were used as templates to elucidate their corresponding protein-protein interaction (PPI) networks using the PPI databases, POINT and POINeT. As a result, 18 genes, of which six were not disclosed in the initial expression profile analysis, were found to be able to serve as the minimal discriminators for distinguishing ESCC tumors from normal specimens. Of these discriminators, ten (BGN, COL1A1, COL1A2, MMP9, CD44, FN1, TGFBI, PXN, SPARC and VWF) were associated with tumor metastasis and formed a highly interactive network with the first four molecules as 'hubs'. Our study not only reveals how novel insights can be obtained from gene expression profiling, but also highlights a group of highly interacting genes associated with metastasis in ESCC.
International Journal of Oncology 01/2009; 34(1):117-28. · 2.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Esophageal laceration with intramural dissection is a rare type of injury but without perforation. It is difficult to differentiate from esophageal perforation at presentation time. We report the case of a 46-year-old man who was admitted to our hospital complaining of progressive chest pain, dysphagia, and odynophagia after swallowing a fish bone three days prior to admission. Esophagoscopy revealed a deep longitudinal laceration with pus discharge in the esophagus. Computed tomography of the chest revealed low posterior mediastinal abscess formation. Surgery was performed under the impression of esophageal perforation. The definite diagnosis was esophageal laceration with intramural dissection.
Interactive cardiovascular and thoracic surgery 10/2008; 7(5):864-5.
-
[show abstract]
[hide abstract]
ABSTRACT: Endobronchial leiomyosarcoma is an unusual tumor of the respiratory tract. Clinically, patients may present with intermittent coughing, chest pain, dyspnea, hemoptysis, and fever until late in the course of the disease because of total obstruction of the main airway. In this paper, we report the case of a 51-year-old male with endobronchial leiomyosarcoma who presented with acute respiratory distress as a result of total obstruction of the right main bronchus and suffocation after massive hemoptysis. After intraoperative bronchoscopic assessment and bronchotomy, an elongated endobronchial tumor was found that arose from the right middle lobe (RML) bronchus with intraluminal extension upward into the right main bronchus. He underwent RML and right lower lobe (RLL) bilobectomy and had a rapid and uneventful recovery.
Annals of thoracic and cardiovascular surgery: official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia 05/2008; 14(2):105-8. · 0.69 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Natural killer (NK) cells are important effector cells in the defense against tumors. The present study retrospectively examines the intratumoral NK cells in primary resected esophageal squamous cell carcinoma (ESCC) and the correlation between the patient' outcome and the intratumoral NK cells infiltration.
Immunohistochemistry was used to analyze the intratumoral NK cell infiltration in 38 archival specimens from patients with primary resected ESCC.
According to the cut-off point of the staining for intratumoral NK cell infiltration, 14 (37%) cases had high level infiltration and 24 (63%) low. The 5-year survival of patients with high level NK infiltration was significantly better than that of patients with a low level of NK infiltration (p < 0.01). Multivariate analysis did not show NK cell infiltration to be a significant prognostic factor.
Intratumoral NK cell infiltration is associated with a favorable outcome in ESCC. Intratumoral NK cell infiltration might be used as a variable with prognostic value in primary resected ESCC.
Chang Gung medical journal 05/2005; 28(5):335-40.
-
Chueh-Chuan Yen,
Yann-Jang Chen,
Chin-Chen Pan,
Kai-Hsi Lu,
Paul Chih-Hsueh Chen, Jiun-Yi Hsia,
Jung-Ta Chen,
Yu-Chung Wu,
Wen-Hu Hsu,
Liang-Shun Wang,
Min-Hsiung Huang,
Biing-Shiung Huang,
Cheng-Po Hu,
Po-Min Chen,
Chi-Hung Lin
[show abstract]
[hide abstract]
ABSTRACT: By using comparative genomic hybridization, gain of 3q was found in 45-86% cases of esophageal squamous cell carcinoma (EC-SCC). Chromosome 3q25.3-qter is the minimal common region with several oncogenes found within this region. However, amplification patterns of these genes in EC-SCC have never been reported. The possible association of copy number changes of these genes with pathologic characteristics is still not clear.
Real-time quantitative PCR (Q-PCR) was performed to analyze the copy number changes of 13 candidate genes within this region in 60 primary tumors of EC-SCC, and possible association of copy number changes with pathologic characteristics was analyzed by statistics. Immunohistochemistry (IHC) study was also performed on another set of 111 primary tumors of EC-SCC to verify the association between TP63 expression change and lymph node metastasis status.
The average copy numbers (+/-SE) per haploid genome of individual genes in 60 samples were (from centromere to telomere): SSR3: 4.19 (+/-0.69); CCNL1: 5.24 (+/-0.67); SMC4L1: 2.01 (+/-0.16); EVI1: 2.02 (+/-0.12); hTERC: 5.28 (+/-0.54); SKIL: 2.71 (+/-0.14); EIF5A2: 1.95 (+/-0.12); ECT2: 9.18 (+/-1.68); PIK3CA: 8.13 (+/-1.17); EIF4G1: 1.07 (+/-0.05); SST: 3.07 (+/-0.25); TP63: 2.51 (+/-0.22); TFRC: 2.42 (+/-0.19). Four clusters of amplification were found: SSR3 and CCLN1 at 3q25.31; hTERC and SKIL at 3q26.2; ECT2 and PIK3CA at 3q26.31-q26.32; and SST, TP63 and TFRC at 3q27.3-q29. Patients with lymph node metastasis had significantly lower copy number of TP63 in the primary tumor than those without lymph node metastasis. IHC study on tissue arrays also showed that patients with lymph node metastasis have significantly lower TP63 staining score in the primary tumor than those without lymph node metastasis.
This study showed that different amplification patterns were seen among different genes within 3q25.3-qter in EC-SCC, and several novel candidate oncogenes (SSR3, SMC4L1, ECT2, and SST) were identified. TP63 is amplified in early stage of EC-SCC carcinogenesis but down-regulated in advanced stage of disease.
World Journal of Gastroenterology 04/2005; 11(9):1267-72. · 2.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The divergences in the clinical significance of bone marrow microinvolvement (BMM) in patients with nonsmall cell lung carcinoma (NSCLC) necessitated a long-term large series study.
Between March 1997 and June 2001, the authors analyzed 212 bone marrow specimens (from the posterior iliac crest) taken from patients with NSCLC before surgery. The degree of tumor differentiation included well differentiated carcinoma in 12 Patients, moderately differentiated carcinoma in 112 Patients, and poorly differentiated carcinoma in 68 Patients. The pTNM staging (according the the criteria of the American Joint Committee on Cancer) included Stage IA in 8 patients, Stage IB in 70 patients, Stage IIB in 36 patients, Stage IIIA in 54 patients, Stage IIIB in 14 patients, and Stage IV in 10 patients. The specimens were evaluated by immunohistochemical staining with antihuman cytokeratin AE1/AE3, Ber-EP4, and clone MNF116 mixed solution to detect the presence of malignant epithelial cells in the bone marrow.
Positive results were observed in 66 patients (34.4%). The occurrence of BMM was not found to be related to patient age, gender, cell type, or TNM status. The 5-year disease-free survival rates were 44.9% and 40.5% in BMM-negative and BMM-positive patients, respectively (P = 0.3797). The 5-year cumulative survival rates were 43.5% and 44.0% in BMM-negative and BMM-positive patients, respectively (P = 0.4262). Multivariate analysis failed to demonstrate BMM as an independent prognostic factor (P = 0.1817).
The results of the current study showed that although BMM was observed frequently in patients with NSCLC, regardless of tumor stage and pathologic types, its occurrence was not a good predictor of long-term prognosis.
Cancer 03/2004; 100(4):794-800. · 4.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The management of ipsilateral multifocal non-small cell lung cancer (NSCLC) in different lobes is still controversial. We analyzed our surgical results and the prognostic factors with the findings of other studies and evaluated the surgical feasibility.
Between January 1, 1983 and December 31, 2001, 1408 patients underwent operation for primary NSCLC, including 20 patients who received complete resections for multifocal NSCLC of the same histological type in ipsilateral different lobes.
The 1-, 2- and 5-year survival rate of the 20 patients were 60.0, 39.3 and 28.1%, respectively. There were no statistically significant differences in T-status, gender, pathological type, and stage. An excellent 5-year survival rate of 66.7% (median, 101 months) in the group without node involvement was found (N0 vs. N1+2, P=0.0872).
Our data suggest that surgical resection is mandatory in patients with ipsilateral multifocal NSCLC when there is no evidence of node metastasis.
European Journal of Cardio-Thoracic Surgery 01/2004; 24(6):1008-12. · 2.55 Impact Factor
-
Chueh-Chuan Yen,
Yann-Jang Chen,
Kai-Hsi Lu, Jiun-Yi Hsia,
Jung-Ta Chen,
Cheng-Po Hu,
Po-Min Chen,
Jin-Hwang Liu,
Tzeon-Jye Chiou,
Wei-Shu Wang,
Muh-Hwa Yang,
Ta-Chung Chao,
Chi-Hung Lin
[show abstract]
[hide abstract]
ABSTRACT: We performed an integrated cytogenetic study using a combination of comparative genomic hybridization (CGH), spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) to analyze chromosomal aberrations associated with 8 human esophageal squamous cell carcinoma (EC-SCC) cell lines, and used real-time quantitative PCR (Q-PCR) to study the copy number changes of two candidate genes of chromosome 3q, PIK3CA and TP63, in 20 primary tumors of EC-SCC. The pooled CGH results revealed frequent gain abnormalities on chromosome arms 1p, 1q, 3q, 5p, 6p, 7p, 7q, 8q, 9q, 11q, 12p, 14q, 15q, 16p, 16q, 17q, 18p, 19q, 20q, 22q, and Xq, while frequent losses were found on 3p, 4, 5q, 6q, 7q, 9p, and 18q. SKY detected 195 translocations, 13 deletions and 2 duplications. Among the 374 breakpoints, most clustered at the centromeric regions, such as 8q10, 13q10, 7q10, 9q10, 14q10, 15q10, 16q10, 21q10, and 22q10, but also at other regions, including 3q (3q21, 3q22, 3q25), 7p (7p22, 7p14, 7p12), 7q (7q21, 7q31, 7q32), 8q (8q21.1, 8q23), 11q (11q21, 11q24), 13q (13q14) and 18q (18q21). There was a good correlation between the number of aberrations identified by CGH and SKY (r=0.667; p=0.035). Combined CGH and SKY analyses indicated that chromosomes 3, 7, 9, 11, 14, 16, 18, 19, 20, and 22 harbored higher frequency of chromosomal aberrations than expected. FISH using BAC clones containing oncogene PIK3CA and TP63 found that both genes were amplified in 6 and 5 cell lines, respectively. Q-PCR analysis of primary tumors revealed amplification of PIK3CA and TP63 in 100% and 80% of the cases. Average copy number of PIK3CA per haploid genome was greater than that of TP63 (6.27 vs 2.73), and the difference showed statistical significance (p<0.001). Combination of CGH, SKY and FISH could reveal detailed chromosomal changes associated with esophageal cancer cells, and Q-PCR could assess the change of the candidate genes in clinical samples in a high throughput way.
International Journal of Oncology 11/2003; 23(4):871-81. · 2.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We evaluate the clinical results of thoracoscopic T3-4 sympathicotomy for axillary osmidrosis.
From July 1995 to June 2001, 262 patients (208 females, 54 males) with axillary osmidrosis have been treated by thoracoscopic T3-4 sympathicotomy. All patients were followed up for a minimum of 10 months (average 42 months). The patients were evaluated by telephone or mail questionnaires. The results were categorized as excellent, good, fair, or poor.
There were no surgical mortalities and major complications in this series. The surgical outcomes were excellent in 144 (55%) patients, good in 39 (15%) patients, fair in 55 (21%) patients, and poor in 24 (9%) patients. Compensatory sweating developed in 171 (65%) patients. Dry hands developed in 40 (15%) patients.
Thoracoscopic T3-4 sympathicotomy is a safe, fast, cosmetic, and effective method in treating axillary osmidrosis.
European Journal of Cardio-Thoracic Surgery 10/2003; 24(3):425-7. · 2.55 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The present study retrospectively examines the expression of caspase-3 in primary resected esophageal squamous cell carcinoma (ESCC) and the correlation between the outcome of patients and the expression of proteins.
Immunohistochemistry and Western blot analyses were used to analyse the expression of caspase-3 in 40 archival specimens of patients with primary resected ESCC.
According to our cut-off point of the staining for caspase-3, 24 (60%) cases were positive and 16 (40%) negative. Caspase-3 expression correlated with a significant favorable prognosis in primary resected ESCC (P=0.02). A multivariate analysis of clinical and biological factors indicated that stage, tumor differentiation, and caspase-3 expression were independent prognostic factors.
Caspase-3 expression might be a good and new prognostic indicator for primary resected ESCC.
European Journal of Surgical Oncology 03/2003; 29(1):44-8. · 2.50 Impact Factor
-
Chueh-Chuan Yen M.D,
Ph.D. Yann-Jang Chen M.D,
Jung-Ta Chen M.D,
Jiun-Yi Hsia M.D,
Ph.D. Po-Min Chen M.D,
Ph.D. Jin-Hwang Liu M.D,
Ph.D. Frank S. Fan M.D,
Tzeon-Jye Chiou M.D,
Wei-Shu Wang M.D,
Ph.D. Chi-Hung Lin M.D,
Chueh‐Chuan Yen,
Yann‐Jang Chen,
Jung‐Ta Chen, Jiun‐Yi Hsia,
Po‐Min Chen,
Jin‐Hwang Liu,
Frank S. Fan,
Tzeon‐Jye Chiou,
Wei‐Shu Wang,
Chi‐Hung Lin
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND
Esophageal carcinoma is a major cause of cancer-related deaths among males in Taiwan. However, to date, the genetic alterations that accompany this lethal disease are not understood.METHODS
Chromosomal aberrations of 46 samples of esophageal squamous cell carcinoma (EC-SCC) were analyzed by comparative genomic hybridization (CGH), and their correlations with pathologic staging and prognosis were analyzed statistically.RESULTSIn total, 321 gains and 252 losses were found in 46 tumor samples; thus, the average gains and losses per patient were 6.98 and 5.47, respectively. Frequent gain abnormalities were found on chromosome arms 1q, 2q, 3q, 5p, 7p, 7q, 8q, 11q, 12p, 12q, 14q, 17q, 20q, and Xq. Frequent deletions were found on chromosome arms 1p, 3p, 4p, 5q, 8p, 9p, 9q, 11q, 13q, 16p, 17p, 18q, 19p, and 19q. It was found that deletions of 4p and 13q12–q14 and gain of 5p were significantly correlated with pathologic staging. Losses of 8p22-pter and 9p also were found more frequently in patients with advanced disease. Gain of 8q24-qter was seen more frequently in patients with Grade 3 tumors. A univariate analysis found that pathologic staging; gains of 5p and 7q; and deletions of 4p, 9p, and 11q were significant prognostic factors. However, pathologic staging became the only significant factor in a multivariate analysis.CONCLUSIONSCGH not only revealed novel chromosomal aberrations in EC-SCC, but also found possible genotypic changes associated with disease progression. Despite all of the possible associations of chromosomal aberrations with disease progression, the most important prognostic factor for patients with EC-SCC was pathologic staging. Cancer 2001;92:2769–77. © 2001 American Cancer Society.
Cancer 11/2001; 92(11):2769 - 2777. · 4.77 Impact Factor
